This Week in HIV Research: So Many Relative Risks
Our attempts to quantify the significance of comorbidities among people living with HIV can all-too-easily descend into a mind-numbing jumble of numbers with less-than-clear clinical relevance. We know that living with HIV—and, sometimes, taking certain HIV medications—can increase a person’s risk for a number of different adverse health outcomes, but when we try to put a finger on precisely what that risk is, the answer can be elusive.
Then again, maybe it’s enough to know that a significant relative risk exists, and use that knowledge to counsel our patients and work to mitigate known risk factors. Take our four study selections this week, for example; while each of them puts numbers on a particular risk in people living with HIV (PLWH), perhaps it’s enough to learn that:
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Bone fracture risks are definitively higher among people with HIV, particularly among certain subgroups.
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People who switch to tenofovir alafenamide (TAF) often fall into a worse classification level for some lipid values over the following months.
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A measure of pulmonary function is more likely to be impaired in HIV-positive men who have sex with men (MSM) than HIV-negative MSM.
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Taking immunomodulatory drugs—particularly checkpoint inhibitors—can trigger a viral load blip.
But hey, if you want to get into some of those numbers, who are we to say no? Let’s dive in. To beat HIV, you have to follow the science!
Bone Fracture Risk Significantly Higher in PLWH Than General Population
PLWH have a 1.9 times higher risk of bone fracture compared to the general population, a meta-analysis published in PLOS One found. The findings offer a concrete reminder of the clinical risks associated with increased rates of bone loss among people living with HIV.
All studies included in the meta-analysis were conducted in high-income countries; only reports published in English were included. In total, the review comprised 21 studies involving more than 300,000 participants.
Among people living with HIV, the risk of breaking a bone was found to be greatest among older people, people who smoked cigarettes, people coinfected with hepatitis C (HCV), and people suffering from osteoporosis. (Several of the individual studies also found some or all of these risk factors.)
The fracture risk in this meta-analysis was higher than that found in a separate study of postmenopausal women, which had found the risk to be 1.5 times greater in women living with HIV than HIV-negative women. That difference could be explained by the inclusion of men in the current study, its authors wrote.
While some of the risk factors for fractures are unavoidable, such as age, others can be modified, the authors wrote. To that end, they recommended that HIV care providers prioritize referrals to smoking cessation programs and promptly initiate HCV therapy in people who are coinfected.
Switching to TAF Often Worsens Lipid Profile Classification
The potential effect of tenofovir alafenamide (TAF) on lipid parameters should be a factor in not only considering a switch from tenofovir disoproxil fumarate (TDF), but also when considering a first-line antiretroviral regimen, the authors of a study published in AIDS cautioned.
The prospective study, which took place in Dublin, Ireland, included 238 real-world cases in which participants switched from a prior regimen to one containing TAF. After a median 24 weeks post-switch, 37% of 194 participants had a low-density lipoprotein (LDL) level that was considered “abnormal” or “very high abnormal” based on the National Cholesterol Education Program-Adult Panel III (NCEP-ATP III) classification, compared to 24% of participants at baseline.
Similarly, 16% had a total cholesterol level that was classified as “abnormal” or worse after switching to TAF, compared to 5% before starting TAF. Triglycerides and high-density lipoproteins (HDL) did not change significantly after changing treatment regimens. The 24% of participants who were already taking lipid-lowering medications before they switched to TAF saw less of an effect on their lipid parameters.
Since 85% of participants who switched to TAF had been taking TDF at baseline, it is unclear whether the observed results were due to a loss of the protective effect of TDF on lipids, or whether they were caused by TAF directly affecting cholesterol metabolism, study authors noted. They called for additional data on this question.
Meanwhile, “[d]evelopment of dyslipidemia should be taken into consideration alongside renal and bone safety when choosing between TDF and TAF,” they concluded.
Impaired Gas Exchange in Lungs of MSM Living With HIV
MSM who are living with HIV appear to perform worse than HIV-negative men in at least one type of pulmonary function test, researchers recently concluded in a study published in AIDS.
The current study focused on two lung tests: spirometry (measured as FEV1), which assess airflow obstruction, and single-breath diffusing capacity for carbon monoxide (measured as DLCO), a measure of gas exchange in the lungs. A total of 1,067 MSM were included in the study, 591 of whom were living with HIV.
Although FEV1 predicted values did not differ significantly based on serostatus (they came close to, but did not meet, the threshold for statistical significance), DLCO predicted values did—and MSM living with HIV were more likely to have DLCO impairment. This is significant in part because DLCO might be a better indicator of lung function in PLWH than the more common spirometry, study authors wrote.
While many statistical associations with HIV-specific variables were of borderline significance, it appeared that worse DLCO was associated with longer antiretroviral exposure—i.e., in people who began HIV treatment in an early era. (Study data came from the Multicenter AIDS Cohort Study, which has been enrolling since 1984.) A post-hoc analysis also showed that nadir CD4 count was related to worse gas exchange in both current and former smokers living with HIV.
Study authors cautioned against overinterpreting these findings, but noted the complex relationship between lung function, HIV status, antiretroviral therapy, cigarette smoking, and immune function indicated by the data. They plan to follow the cohort longitudinally and called for prioritizing research on the possible causes of the observed risk of lung impairment in PLWH.
Immunomodulatory Drugs Associated With Viral Blips, But Not HIV Treatment Failure
PLWH can safely take immunomodulatory drugs (IMDs), but viral blips are more likely, a retrospective cohort study published in AIDS showed.
The study analyzed data on 77 PLWH who experienced a total of 110 treatment episodes in which they received medications that affect the immune system. (Such drugs are usually prescribed for autoimmune, non-HIV inflammatory, and oncologic conditions.) In 51 of those episodes, the person began taking IMDs while their viral load was undetectable. Over the next year, no virologic failures occurred, but in 21 episodes (41%) the person experienced a viral load blip—usually to a level that was still below 200 copies/mL.
Viral blips were especially likely in participants who had been prescribed checkpoint inhibitors. That type of drug can reverse HIV latency, which may explain that result, the authors wrote.
While most participants were on antiretroviral therapy when they started immunomodulatory treatment, two people were living with undiagnosed HIV and four participants seroconverted while taking IMDs. The cohort also included four elite controllers—i.e., people whose HIV viral load remains suppressed in the absence of antiretroviral treatment.
Study authors called for further research into this topic, including an HIV-negative control group. Meanwhile, they recommended that providers do the following before starting immunomodulatory treatment:
- Test for HIV.
- Counsel PLWH about the limited safety data available.
- Test patients with HIV for tuberculosis and viral hepatitis.
- Consult with the patient’s HIV care providers.
In addition, once the immunomodulatory medication has been prescribed, providers should monitor quarterly viral load results and consult with a patient’s HIV provider if necessary, the authors wrote. If people seroconvert while on immunomodulatory drugs, they should be referred to an HIV provider to start antiretroviral therapy promptly.